Method for evaluating and predicating toxicity and efficacy of medicament by using metabonomic technology

A metabolomics and metabolite technology, which is applied in the field of application of metabolomics technology to evaluate and predict drug toxicity and efficacy, and can solve problems such as the elimination of exogenous metabolite signals.

Inactive Publication Date: 2012-02-01
SICHUAN YUANDASHUYANG PHARM CO LTD
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Problems solved by technology

[0007] However, there is no report in the prior art that eliminates the exogenous metabolite signal from the sample detection signal of the drug administration group to accurately obtain the endogenous metabolite signal, and evaluates the toxicity and efficacy of metabolomics drugs

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  • Method for evaluating and predicating toxicity and efficacy of medicament by using metabonomic technology
  • Method for evaluating and predicating toxicity and efficacy of medicament by using metabonomic technology
  • Method for evaluating and predicating toxicity and efficacy of medicament by using metabonomic technology

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Embodiment 1

[0087] In order to realize the drug efficacy and toxicity evaluation of the present invention, it is necessary to eliminate the chromatographic baseline drift of one of the two types of interference signals included in the signal matrix obtained by HPLC-MS / MS detection of biological samples, and the present invention proposes an elimination method. In order to prove the feasibility of the method, a standard sample system was designed in this embodiment, and at the same time, a CCl4-induced hepatotoxic SD rat urine sample signal was used for verification, which is now explained as follows:

[0088] Standard sample system: for the chromatograms of three mixed standard samples such as blank control group, drug administration group and exogenous substances (attached figure 1 ), follow the steps below to eliminate chromatographic baseline drift:

[0089] I) In the signal matrix with the retention time Rt and the mass-to-charge ratio m / z as the row-column index or column-row index, ...

Embodiment 2

[0095] In order to realize the drug efficacy and toxicity evaluation of the present invention, it is necessary to eliminate the exogenous metabolite signal, one of the two types of interference signals included in the signal matrix obtained by HPLC-MS / MS detection of biological samples, the present invention proposes two a method of elimination. In order to prove the feasibility of the method, the standard sample system of the system described in Example 1 was used in this embodiment, and at the same time, another simulation system was designed for verification, which is now described as follows:

[0096] Simulation system: see attached Figure 6 , the figure shows that endogenous and exogenous metabolites have obvious signal overlap, which is difficult to eliminate by common methods. Utilize the method for eliminating exogenous metabolite signals described in the summary of the invention—"mass spectrometry signal orthogonal projection method" to obtain the endogenous metabol...

Embodiment 3

[0107] The experimental SD rats were randomly divided into the blank control group and the xanthate subgroup, and the water extract of the Chinese medicine xanthate subgroup was administered to the rats (60g / kg) repeatedly, for 3 consecutive days, twice a day, and the collection time was 0-24h. , 24h~48h, 48h~72h urine; the normal group was given corresponding doses of distilled water, and collected 0~24h, 24h~48h, 48h~72h urine for 3 consecutive days; urine samples were precipitated with methanol to remove protein, and centrifuged at 12000rpm After 5 minutes, the supernatant was filtered through a 0.45 μm microporous membrane, and the sample measurement signal matrix was obtained by HPLC-MS / MS (the retention time Rt is the row index, and the mass-to-charge ratio m / z is the column index). Three days after administration, the xanthate subgroup and the normal control group were anesthetized by intraperitoneal injection of 4% chloral hydrate (1ml / 100g body weight), blood samples w...

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Abstract

The invention relates to a method for evaluating and predicating the toxicity and the efficacy of a medicament based on an endogenous metabolism signal which is acquired by eliminating an exogenous metabolism signal in a biological sample, in particular to the method for evaluating and predicating the specific toxicity and the non-specific toxicity of the medicament by using a metabonomic technology. In the method, the biological sample depended by a metabolism group is obtained according to a blank control group, a model toxic substance group and a toxicity test group which are set in the metabolism group; and a sample measuring signal matrix is detected and acquired for evaluating and predicating the toxicity of the medicament. The invention simultaneously discloses a method for evaluating and predicating the efficacy by using the metabonomic technology. In the method, a biological sample depended by the met toxic substance group, a treatment group and a positive medicament control group which are set in the metabolism group; and a sample measuring signal matrix is detected and acquired for evaluating and predicating the efficacy of the medicament. According to the methods disclosed by the invention, the toxicity and the efficacy of the medicament can be evaluated more comprehensively and accurately.

Description

technical field [0001] The invention relates to a method for accurately obtaining endogenous metabolite signals by eliminating exogenous metabolite signals in biological samples, and evaluating and predicting the toxicity and efficacy of metabolomics drugs based on the endogenous metabolite signals. Background technique [0002] Drug toxicity and efficacy evaluation methods are mainly based on certain reactions of experimental animals to drugs to evaluate the toxicity and efficacy of drugs. For this evaluation method, the traditional method can only use one or several indicators to characterize its drug efficacy and toxicity, which lacks an overall comprehensive evaluation, and has low sensitivity to toxicity and drug efficacy. For low toxicity drugs, even subtoxic drugs (especially for traditional Chinese medicine), it is impossible to evaluate their toxicity, which eventually leads to some unexpected toxic and side effects when some drugs enter clinical trials or enter cli...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G06F19/00G01N30/72G01N27/62
Inventor 谢洪平牟红元吕天
Owner SICHUAN YUANDASHUYANG PHARM CO LTD
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